The imaginary hybrid drug PROFOX is an anxious prediction of a therapeutic
disaster for post menopausal women who need treatment for low bone density,
depression , pelvic atrophy and vasomotor symptoms but are denied estrogens.

Physicians and psychiatrists have been slow to accept the clear benefits
of estrogen therapy in the treatment of osteoporosis and depression. Is
it an honest fear of side effects, ignorance of hormone therapy, misinterpretation
of the data or simply a territorial hold on the condition which then condemns
women to sub optimal therapy?

Although estrogens have been proven to prevent fractures in a mixed risk
population and that the benefits on bone density and histology are dose
dependant it has been relegated to a treatment to be used if others fail
or if the woman has severe menopausal symptoms. This protection from estrogens
effects not only the skeleton but also the intervertebral discs which make
up one quarter of the length of the spinal column. This latter benefit is
not produced by bisphosphanates. This failure of physicians to familiarise
themselves with estrogen therapy has, in their minds, been justified by
the results of the WHI study and by the regulatory bodies who have advised
that estrogen should not be first choice therapy for osteoporosis. But in
reality the physicians objections to estrogen therapy antedated the WHI
study by many years. Specialists are a product of their training which for
non gynaecologists does not include the subtleties of the use , the dose
and route of various estrogens , gestogens and occasionally androgens.

Updated information and interpretation of the WHI study indicates that
HRT, particularly estrogen alone, is both safe and protective in the younger
postmenopausal woman below the age of 60. Such therapy is associated with
fewer fractures , less colon cancer , fewer heart attacks , possibly less
breast cancer and certainly fewer deaths. It should, in the minds of many
workers, be first line therapy in this situation. However, Fosamax Once
Weekly is an inexpensive alternative recommended by NICE as first line therapy
and preferred by physicians. It produces lesser skeletal and systemic benefit
than estrogens but it does not confuse the medical attendant with hormonal
side effects such as bleeding, mastalgia and occasional PMS symptoms. These
are problems that can be dealt with by any competent general practitioner
but have not been learned by specialist bone physicians and rheumatologists
who also seem to be complacent about considerable long term side effects
of bisphosphanates.

A similar ‘turf war’ occurs with the commonplace depression
in perimenopausal women. These women with estrogen responsive depression
often have a history of postnatal depression and premenstrual depression
which have all been shown to be effectively treated by transdermal estrogens
in good controlled trials in the most prestigious journals . It is therefore
surprising that none of these studies have been repeated by those mostly
responsible for the treatment of depression in women. This neglect is either
due to the unlikely belief that these studies are perfect or because psychiatrists
and the pharmaceutical industry do not want to show the benefits or even
the superiority of estrogens. For example there is only one placebo controlled
study demonstrating that transdermal estrogens are effective in treating
severe premenstrual depression by suppressing ovulation but there are now
50 similar studies showing that SSRIs are useful. Why should the industry
fund studies that reveal that their high profit in patent drug is less effective
than the much less profitable estrogens?

Psychiatrists almost invariably refuse to accept these data relying upon
psycho therapy , SSRI’s and even ECT particularly in the private sector.
Once again it is to the disadvantage of the women that psychiatrists have
not chosen to become aware of this modality of treatment. It is commonplace
to see women with perimenopausal depression who have been taking many mood
stabilizing drugs for many years .They claim to have been last well during
their last pregnancy after which they started or recommenced antidepressants
for post natal depression , later pre menstrual depression and climacteric
depression. It is difficult to obtain precise data but antidepressants are
now used by about 30% percent of women in the UK and there is even a move
to use this drug for the treatment of vasomotor symptoms. It is barely effective
but it is becoming a new indication for SSRI therapy.

The nightmare for the future is that postmenopausal women with hot flushes,
depression , sexual problems and low bone density, who need estrogens perhaps
with testosterone, will be given a SSRI and bisphosphanate combination .
PROFOX, a Frankenstein combination of PROzac and FOsamaX . As these two
drugs are now available as cheap generics they are already being prescribed
together. Unfortunately this warning of a single preparation is not a fanciful
aberration as we already have close to the market a combination of a SERM
for osteoporosis combined with oestrogens to prevent the symptoms of oestrogen
deficiency. This was a joke comment at a British Menopause Society debate
10 years ago but has now become a reality. Unless the regulatory authorities
consider the current safety data in the under 60s and modify their resistance
to HRT the spectre of PROFOX will be upon us. It is a vision of the future
which must be avoided.